Table 3.
Comparison of the novel UKALL high hyperdiploid group with double trisomy and triple trisomy definitions proposed by the Children's Oncology Group
| UKALL HeH good risk, n=579 | UKALL HeH good risk and MRD <0·03%, n=377 | Triple trisomy (+4,+10,+17), n=299* | Double trisomy (+4,+10), n=395* | ||
|---|---|---|---|---|---|
| Proportion of high hyperdiploidy cases† | 80% | 60% | 41% | 54% | |
| Sex | |||||
| Female | 278 (48%) | 179 (47%) | 147 (49%) | 198 (50%) | |
| Male | 301 (52%) | 198 (53%) | 152 (51%) | 197 (50%) | |
| US National Cancer Institute risk group | |||||
| Standard | 443 (77%) | 281 (75%) | 229 (77%) | 298 (75%) | |
| High | 136 (23%) | 96 (25%) | 70 (23%) | 97 (25%) | |
| Slow early responders | |||||
| No | 526 (91%) | 350 (93%) | 272 (91%) | 357 (90%) | |
| Yes | 53 (9%) | 27 (7%) | 27 (9%) | 38 (10%) | |
| MRD at end of induction, % | |||||
| <0·03 | 377 (65%) | 377 (100%) | 187/255 (73%) | 247/337 (73%) | |
| ≥0·03 | 202 (35%) | .. | 68/255 (27%) | 90/337 (27%) | |
| Relapse | |||||
| No | 548 (96%) | 364 (97%) | 284/294 (97%) | 372 (95%) | |
| Yes | 25 (4%) | 13 (3%) | 10/294 (3%) | 18 (5%) | |
| Proportion of all HeH relapses | 53% | 28% | 21% | 38% | |
| Outcome rates at 10 years (95% CI) | |||||
| Relapse rate | 5% (3–7) | 4% (2–6) | 4% (2–7) | 5% (3–8) | |
| Event-free survival | 92% (90–94) | 95% (92–97) | 92% (88–94) | 91% (88–94) | |
| Overall survival | 96% (94–97) | 98% (96–99) | 96% (93–97) | 95% (92–96) | |
| Unadjusted HR comparing each group with remaining high hyperdiploid cases | |||||
| Relapse rate | 0·26 (0·15–0·47); <0·0001 | 0·28 (0·14–0·53); <0·0001 | 0·38 (0·19–0·77); 0·0070 | 0·51 (0·28–0·91); 0·024 | |
| Event-free survival | 0·37 (0·23–0·60); <0·0001 | 0·29 (0·17–0·51); <0·0001 | 0·71 (0·44–1·16); 0·176 | 0·74 (0·47–1·18); 0·203 | |
| Overall survival | 0·29 (0·16–0·54); <0·0001 | 0·16 (0·07–0·39), <0·0001 | 0·64 (0·33–1·24); 0·185 | 0·84 (0·46–1·53); 0·56 | |
| HR comparing each group with remaining high hyperdiploid cases adjusted for MRD‡ | |||||
| Relapse rate | 0·26 (0·14–0·48); <0·0001 | 0·31 (0·16–0·60); <0·0001 | 0·41 (0·20–0·86); 0·018 | 0·54 (0·29–1·02); 0·057 | |
| Event-free survival | 0·33 (0·20–0·56); <0·0001 | 0·31 (0·18–0·55); <0·0001 | 0·64 (0·36–1·13); 0·123 | 0·69 (0·41–1·16); 0·164 | |
| Overall survival | 0·23 (0·11–0·48); <0·0001 | 0·18 (0·07–0·44); <0·0001 | 0·47 (0·20–1·11); 0·086 | 0·69 (0·34–1·44); 0·325 | |
| HR comparing each group with remaining high hyperdiploid cases for MRD at end of induction <0·03% | |||||
| Relapse rate | 0·27 (0·12–0·61); 0·0020 | .. | 0·50 (0·20–1·28); 0·149 | 0·53 (0·23–1·23); 0·142 | |
| Event-free survival | 0·29 (0·14–0·59); 0·0010 | .. | 0·69 (0·32–1·46); 0·329 | 0·61 (0·30–1·24); 0·172 | |
| Overall survival | 0·14 (0·05–0·40); <0·0001 | .. | 0·53 (0·17–1·66); 0·276 | 0·57 (0·20–1·60); 0·285 | |
| HR comparing each group with remaining high hyperdiploid cases for MRD at end of induction ≥0·03% | |||||
| Relapse rate | 0·28 (0·11–0·68); 0·0050 | .. | 0·27 (0·08–0·92); 0·037 | 0·50 (0·20–1·26); 0·142 | |
| Event-free survival | 0·41 (0·19–0·91); 0·029 | .. | 0·54 (0·23–1·28); 0·163 | 0·74 (0·34–1·61); 0·453 | |
| Overall survival | 0·39 (0·14–1·10); 0·075 | .. | 0·37 (0·11–1·32); 0·127 | 0·78 (0·28–2·16); 0·639 | |
| Prediction accuracy | |||||
| C-index | 0·64 | 0·66 | 0·60 | 0·59 | |
| Area under the curve | 0·64 | 0·65 | 0·61 | 0·59 | |
Data are n (%), n/N (%), or HR (95% CI); p value, unless otherwise indicated. MRD data were unavailable for 93 patients. HeH=high hyperdiploid. HR=hazard ratio. MRD=minimal residual disease.
*
Derived from UKALL2003.
†
Proportion of all cases with 51–65 chromosomes.
‡
MRD was included in the model as a covariate.